Impact of the combined timing of PD-1/PD-L1 inhibitors and chemotherapy on the outcomes in patients with refractory lung cancer.

Background PD-1/PD-L1 inhibitors in combination with chemotherapy are widely used in clinical practice. However, the ideal combined timing of them has not been fully explored. Methods In this study, simulation experiments to explore the impacts of the combination of anti-PD-1 antibody (anti-PD-1 Ab) on the cytotoxic effects of chemotherapeutic drugs in peripheral blood mononuclear cells were performed. In addition, the effects of the combined timing of PD-1/PD-L1 inhibitors and chemotherapy on efficacy and safety were retrospectively analysed in patients with refractory lung cancer. Results Experiments in vitro showed that administering the anti-PD-1 Ab 3 days after chemotherapy (represented by dicycloplatin) resulted in significantly weaker cytotoxic effects on lymphocytes, compared with administering the anti-PD-1 Ab before or concurrent with chemotherapy. Moreover, data from 64 lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy as a second- or higher-line therapy were retrospectively analysed. The results showed that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy was associated with longer overall survival [17.3 months versus 12.7 months; hazard ratio (HR) = 0.58, 95% confidence interval (CI) 0.28-1.19, P = 0.137 in univariate analysis; HR = 0.36, 95% CI 0.16-0.80, P = 0.012 in multivariate analysis] and a trend of improved progression-free survival (5.1 months versus 4.2 months; HR = 0.81, 95% CI 0.42-1.54, P = 0.512) compared with administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy. Conclusion Our findings suggest that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy is superior to administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy in patients with refractory lung cancer, but this result needs to be further explored by prospective studies.